Biomedical subjects

G Fountzilas

Publications and source records attributed to G Fountzilas.

At least 145 records · Page 8Linked to original sources

PubMed1992

Primary extranodal non-Hodgkin's lymphoma of the head and neck.

Among 387 cases of non-Hodgkin's lymphoma (NHL) treated in our units between January 1977 and December 1990, 52 (13.4%) had primary extranodal (PE) NHL of the head and neck. The median age was 55 years with a M:F ratio of 1.9:1. The most frequent primary site was the tonsil (28 cases), followed by oral cavity, parotid gland, orbit and other sites. The aggressive histological subtypes predominate. 55.2% of the patients were in stage I and 44.8% in stage II of disease. The CR rate was high (94.2%). The 5 years' overall survival rate was 65% and it was influenced mainly by stage (stage I 82.5% vs. 48.7% in stage II). Sex, age and histology did not significantly affect survival rate. Patients with primary Waldeyer's ring involvement (WR group) did not differ significantly from the other primary sites analyzed as a group (non-WR group) in respect to median age, sex distribution, histology and CR rates. They differed, however, in: (1) stage distribution with stage II disease more frequent in the WR group; (2) overall survival and disease-free survival both of which were significantly better in the non-WR group; and (3) the high incidence of GI tract involvement as initial manifestation of relapse in the WR group. It is concluded that the behaviour of the Waldeyer's ring PE-NHL is rather distinctive and should be considered separately from the other PE-NHL of the head and neck.

Adult↗

PubMed1991

Carboplatin, continuous infusion fluorouracil and mid-cycle high-dose methotrexate as initial treatment in patients with locally advanced head and neck cancer. Hellenic Co-operative Oncology Group Study.

Forty-nine patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with 3 cycles of induction chemotherapy prior to definitive local treatment (surgery and/or radiation therapy). Chemotherapy consisted of carboplatin 300 mg/m2 on day 1, fluorouracil 1000 mg/m2 daily as a continuous infusion on days 1 to 5 and high-dose methotrexate 1.2 g/m2 with leucovorin rescue on day 14. After completing the induction chemotherapy, 9 patients (18%) achieved a complete remission (CR), 26 (54%) a partial remission (PR), 7 had stable disease and 7 a progression. The response rates increased to 53% CR and 18% PR following locoregional treatment. Survival at 12 months was 61% and its actuarial probability at 24 months 31%. Median time to progression was 14 months. Toxicity from chemotherapy was generally mild. Nausea was observed in 35%, vomiting in 26%, stomatitis in 57%, anemia in 22%, leukopenia in 36%, thrombocytopenia in 26% and diarrhea in 6% of the patients. In conclusion, the combination of carboplatin, 5-day continuous-infusion fluorouracil and mid-cycle high-dose methotrexate is a moderately effective, well tolerated regimen in patients with SCCHN but does not seem superior to the combination of carboplatin and fluorouracil only.

Aged↗

PubMed1991

High-dose epirubicin as a single agent in the treatment of patients with advanced breast cancer. A Hellenic Co-operative Oncology Group study.

Fifty-two women with advanced breast cancer were treated with 6 cycles of epirubicin. Even though the study was started with a dose schedule of 110 mg/m2 every 3 weeks, the average treatment interval was 26 days and the median weekly dose 78% of the protocol requirement. Forty-eight patients were evaluable for response; 3 achieved a complete remission which lasted for 17, 24 and 65 weeks, respectively, and 14 a partial remission. Median survival was 32 weeks. Toxicity included nausea/vomiting (68%), anemia (24%), leukopenia (37%), thrombocytopenia (8%), alopecia (81%), stomatitis (24%), diarrhea (14%), fever (19%) and fatigue (14%). Also 1 treatment-related death occurred and 2 cases of arrhythmia. Monotherapy with high doses of epirubicin has definite activity in advanced breast cancer and deserves further study in combination with hematopoietic growth factors which might allow a higher dose intensity.

Adult↗

PubMed1991

Laryngeal preservation in cases of advanced laryngeal cancer treated with platinum based induction chemotherapy before local treatment.

In this study we analyse our preliminary results after treating 28 patients with locally advanced laryngeal cancer with platinum based induction chemotherapy followed by radiation therapy or surgery. The median age of our patients was 60 (46-75) years and median performance status was 80 (60-100). In 18 of the 28 patients locoregional treatment was radiation therapy with an overall response of 94.4 per cent. After a median follow-up of 26 (15-40) months 39.3 per cent of the whole group of patients are alive and disease-free and six (21.4 per cent) patients are alive and disease-free preserving their larynx. We conclude that although more extensive studies with large groups of patients and longer follow-up is needed to reach definite conclusions, it seems that platinum based induction chemotherapy can be used successfully in locally advanced laryngeal cancer followed by radiotherapy. In those cases who respond well, the patient's larynx is preserved without compromizing the overall survival.

Aged↗

PubMed1991

Platinum-based induction chemotherapy followed by radiation as definitive treatment for patients with locally advanced cancer of the oral cavity, oropharynx and hypopharynx. A retrospective analysis of 32 cases.

Thirty-two patients with locally advanced cancer of oral cavity, oropharynx and hypopharynx were treated with three cycles of platinum-based induction chemotherapy followed by radiation therapy. After completion of the combined treatment 50% of the patients were in complete response (CR) and 28% in partial response (PR). So far, 24 patients have died. Local progression occurred in 20 patients. Survival is 29% at 24 months. Seven (22%) patients remain alive and have been disease-free for 22-59 months. In conclusion, induction chemotherapy followed by radiation therapy may omit radical surgery, without compromising survival, in some patients with locally advanced cancer of the oral cavity, oropharynx and hypopharynx.

Adult↗

PubMed1991

Platinum-based chemotherapy followed by radiation therapy of locally advanced nasopharyngeal cancer. A retrospective analysis of 39 cases.

A retrospective analysis was performed of 39 patients with locally advanced nasopharyngeal cancer treated with combined chemotherapy and radiation therapy during the last five years at our departments. There were 26 men and 13 women with median age 55 (24-75) years. Histology was squamous cell carcinoma in 6 patients and undifferentiated carcinoma in the remaining 33 patients. Induction chemotherapy consisted of either regimen A (cisplatin 100 mg/m2 day 1, 5-FU 1,000 mg/m2 days 2-6 as continuous infusion, bleomycin 15 mg days 15 and 29 i.m., mitomycin 4 mg/m2 day 22 and hydroxyurea 1,000 mg/m2 daily days 23-27) or regimen B (carboplatin 300 mg/m2 day 1, 5-FU 1,000 mg/m2 days 1-5 as continuous infusion and methotrexate 1.2 g/m2 day 14 with leucovorin rescue). After completion of induction chemotherapy 13 patients (33%) had complete remission (CR) and 19 (49%) partial remission (PR). The CR rate was increased after radiation therapy to 72%. Survival rates were 88% at 12 and 78% at 24 months. Median time to progression was 29.5 months. In conclusion, induction chemotherapy with a platinum-based regimen followed by radiation therapy achieved a high rate of local control. If the treatment also prolongs survival must, however, be studied by randomized trials.

Adenocarcinoma↗

PubMed1990

Induction chemotherapy with a new regimen alternating cisplatin, fluorouracil with mitomycin, hydroxyurea and bleomycin in carcinomas of nasopharynx or other sites of the head and neck region.

Sixty-six patients with locally advanced (Stages III and IV) carcinoma of the head and neck were treated with three cycles of induction chemotherapy, consisting of cisplatin, fluorouracil (FU) infusion, bleomycin, mitomycin, and hydroxyurea, followed by radiotherapy and/or surgery. There were 48 men and 18 women with a median age of 55 years (range, 18 to 75 years) and Karnofsky performance status of 80 (range, 40 to 90). Primary site was nasopharynx (28 patients), followed by larynx (12) and others (26). Forty-one (62%) patients were presented with Stage IV disease. The response rate to induction chemotherapy was 27% complete response, 50% partial response, 20% stable disease, and 3% progressive disease. There was no significant difference in response rate between patients with cancer of nasopharynx or other sites (P greater than 0.1). Survival was 61% at 24 months. Patients with cancer of nasopharynx had a better survival than those with other primaries (P = 0.033). Toxicities from chemotherapy included alopecia (73%), nausea/vomiting (66%), leukopenia (54%), stomatitis (36%), anemia (32%), thrombocytopenia (16%), and diarrhea (9%). Grade IV toxicity was not observed. Induction chemotherapy with this new regimen resulted in a high response rate but may not be superior to cisplatin and FU alone. It can be safely combined with radiotherapy as a potentially curative therapy in squamous cell carcinoma of the head and neck. Chemotherapy followed by radiation therapy may yield survival similar to radical surgery in laryngeal and other head and neck cancers.

Adult↗

PubMed1990

Schedule-dependent interaction of cytarabine plus doxorubicin or cytarabine plus mitoxantrone in acute myelocytic leukemia cells in culture.

Schedule-dependent interaction of 1-beta-D-arabinofuranosylcytosine (ara-C, cytarabine) plus doxorubicin or ara-C plus mitoxantrone was studied in vitro using HL-60 human acute myelocytic leukemia cell line. The cells were exposed for 1 hr to each drug simultaneously, or sequentially (up to a 28-hr interval), and cell kill effects were determined by clonogenic assay. The results were compared with controls in which cells were exposed to the individual drug only and seeded after appropriate intervals. Simultaneous exposure to two drugs produced lethal effects, but no more than those produced by doxorubicin or mitoxantrone alone. Ara-C followed by doxorubicin produced time-dependent increases in cell kill that was parallel to the doxorubicin alone control, indicative of no true potentiation. In contrast, ara-C followed by mitoxantrone produced striking increases in cell kill effects. Thus, ara-C followed by mitoxantrone resulted in more than 10-fold increases in cell kill at the intervals of greater than or equal to 8 hr between exposures, and the strong cell kill effects were maintained. Our data indicate that: (a) simultaneous exposure to ara-C and doxorubicin or mitoxantrone is less than additive; (b) ara-C followed by doxorubicin is probably only additive; and (c) ara-C followed by mitoxantrone is more than additive, and cell kill effects are sustained.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

Induction chemotherapy with cisplatinum, 5-fluorouracil, bleomycin, mitomycin C and hydroxyurea for previously untreated locally advanced squamous cell carcinomas of the head and neck.

Fifty-three patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with a combined modality treatment consisting of three cycles of induction chemotherapy before definitive surgery and/or radiotherapy. Two additional cycles of the same chemotherapy were given after local-regional therapy. The chemotherapeutic regimen included cisplatinum 100 mg/m2 on day 1, 5-fluorouracil 1000 mg/m2 as a continuous infusion on days 2-6, bleomycin 15 units i.m. on days 15 and 29, mitomycin C 4 mg/m2 i.v. on day 22 and hydroxyurea 1000 mg/m2 p.o. on days 23-27. Each cycle was repeated every 42 days. Forty-nine patients are evaluable for response. There were 37 men and 12 women, with a median age of 58 years (range 18-75 years) and performance status of 80 (range 40-90). Sixteen patients (33%) demonstrated a complete response, 20 (41%) a partial response, yielding a 74% response rate to induction chemotherapy; 12 (24%) patients had stable disease and 1 (2%) progressive disease. The actuarial survival of those patients who completed the whole treatment program was 65% at 2 years and 47% at 3 years. Toxicities included nausea and vomiting (66%). anemia (34%), leukocytopenia (54%), thrombocytopenia (22%), stomatitis (36%), diarrhea (10%), alopecia (78%), hear impairment (4%) and transient creatinine elevation (2%). The results of the present study showed that induction chemotherapy with the above regimen produced a high rate of complete responses and can be safely combined with local-regional therapy to improve local tumor control and increase disease-free survival in patients with locally advanced SCCHN.

Adolescent↗

PubMed1988

Multimodality treatment of non-small cell lung cancer: response to cisplatin, VP-16, and 5-FU chemotherapy and to surgery and radiation therapy.

Twenty-one patients with unresectable non-small cell lung cancer (NSCLC), 11 with stage III M0, five with malignant pleural effusion, and five with a single resectable metastasis were treated with multimodality therapy. All received two to three cycles of preoperative chemotherapy with a new sequential combination of cisplatin (50 mg/m2 IV X 1) followed by 5-FU infusion (40 mg/m2/hr X 72) and etoposide (80 mg/m2/day X 3). Thirteen of 21 (62%) had a partial response, and three (14%) had a minor response to chemotherapy. Of the 19 who underwent surgical exploration, 17 were confirmed to have NSCLC. Ten patients with NSCLC and one with choriocarcinoma were rendered disease free by resection of the primary tumor and lymph nodes. Six received intra- and/or perioperative interstitial therapy with 125I and/or 192Ir. Another patient was treated with 32P. Postoperative external radiotherapy was administered in 15 patients, and adjuvant chemotherapy was administered in ten. This multimodality therapy was well tolerated, safe, and highly effective, resulting in excellent palliation even in patients with pleural effusion and metastasis. The most promising results were in unresectable stage III M0 with a partial response rate of 82% following neoadjuvant chemotherapy and a complete response rate of 73% after surgery. In this group, median survival has not yet been reached and will exceed 12 months.

Adult↗

PubMed1988

[Combined therapy of locally advanced squamous epithelial cancers in the area of the head and neck].

In an effort to improve treatment results in locally advanced squamous cell carcinoma of head and neck, we designed a multimodality treatment programme consisting of three cycles of inductive chemotherapy, after 2-3 weeks loco-regional therapy (surgery and/or radiotherapy), two more cycles of adjuvant chemotherapy with the same regimen were given finally. The chemotherapeutic regimen included cis-platinum 100 mg/m2 on day 1, 5-fluorouracil 100 mg/m2 on days 2-6 as a continuous infusion, bleomycin 15 units on days 15, 29; mitomycin-C 4 mg/m2 on day 2 and hydroxyurea 100 mg/m2 on days 22-26. From August 1984 onwards, 37 patients entered in this study. The group included 31 men and 6 women with a medium age of 54 (18-71) and a performance status of 80 (60-90). Primary sites were nasopharynx (13), oropharynx (5), hypopharynx (3), sinus (3), ethmoids (2), tongue (2), floor of the mouth (2), larynx (6) and unknown (1). 25 patients received 3 cycles of induction therapy whereas 22 completed the whole treatment programme. Following induction therapy, 28% of the patients demonstrated histologically confirmed CR, 40% PR and 32% SD, while after the full multimodality therapy 59% demonstrated CR, 36% PR and 5% SD. Follow-up is 9-36 months. Actual survival at 3 years is 80% for those with a CR post loco-regional therapy. Toxicities were leukopenia (40%), thrombocytopenia (20%), anaemia (40%), nausea and vomiting (60%), stomatitis (52%) diarrhoea (16%) and alopecia (79%). There was one death related to chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1987

Toxicity of FED chemotherapy in non-small-cell lung cancer.

Twenty-eight patients with metastatic and/or recurrent non-small-cell lung cancer were treated with a new sequential combination of escalating doses of cisplatin (50, 75, and 100 mg/m2 IV X 1) followed by 5-FU infusion (40 mg/m2/hour X 72) and etoposide (80 mg/m2/day X 3). Three patients received concurrent external radiation therapy. Eleven of the 28 (39%) had a partial response to chemotherapy. Four others had a minor response. One partial responder became a complete responder by surgical excision of residual cancer. Median time to response was 6 weeks followed by a median response duration of 4 months. In responders, chemotherapy was discontinued at the time of maximal response. Median survival was 7 months. Chemotherapy was well tolerated with absence of leucopenia, thrombocytopenia, and nausea and vomiting in a majority of courses. The common toxicities were alopecia (100%), leucopenia (35%), nausea and vomiting (30%), and electrolyte imbalances (27%). Reversible nephrotoxicity, thrombocytopenia, anemia, mucositis, and diarrhea were infrequent. The response rate in stage IV was less than in stage III. The combination of moderate doses of cisplatin, 5-FU infusion, and etoposide provides a new palliative chemotherapy that is well tolerated with concurrent/sequential radiation therapy and may be useful in the multimodality treatment of non-small-cell lung cancer.

Adult↗

PubMed1987

Combination chemotherapy with prednimustine, adriamycin, vincristine (VAP) in advanced breast cancer. A phase II study.

The purpose of this study was to evaluate VAP combination chemotherapy in advanced breast cancer: prednimustine 80 mg/m2 p.o. days 1-5, adriamycin 40 mg/m2 and vincristine 1.4 mg/m2 1st day in cycles of 3 weeks. Twenty-one women entered the study and 19 were evaluable. The mean age was 54.5 years (25-69) with an average performance status of 60 according to Karnofsky. Hormonal receptors were unknown in 10, positive in 6 and negative in 3. The dominant site of disease was soft tissues in 11, bones in 1, liver in 3 and lung in 4. Fourteen patients had as prior treatment cyclophosphamide, methotrexate and 5-fluorouracil (CMF), two had tamoxifen and three none. Ten patients (52.6%) had a partial response with a mean survival of 7.8+ months, 5 patients (26.3%) had stable disease with a mean survival 6.6+ months and 4 patients (21.1%) had progressive disease with a mean survival of 3 months. Regarding toxicity all patients had alopecia, most of the patients had nausea grade I, whereas 5 patients developed mild leukopenia. We conclude that VAP is an effective, well tolerated chemotherapy combination in patients with advanced breast cancer which deserves further clinical trials.

Adult↗

PubMed1986

Comparison of mitoxantrone and ametantrone in human acute myelocytic leukemia cells in culture and in bone marrow granulocyte-macrophage progenitor cells.

The cytocidal effects of mitoxantrone and ametantrone were compared in 3 human acute myelocytic leukemia (AML) cell lines by means of clonogenic as well as cell growth inhibition assay. The effects of these two agents were also compared on normal bone marrow granulocyte-macrophage progenitor cells (CFU-GM). Mitoxantrone was 10-20 fold more potent against AML cells than ametantrone. Longer exposure of cells to these agents resulted in increased cell kill, but with lesser efficiency. Both mitoxantrone and ametantrone were more cytocidal on normal bone marrow CFU-GM than on AML cells; mitoxantrone was approximately 2.5-fold and ametantrone nearly 10-fold more active against CFU-GM than against HL-60 AML cells.

Anthraquinones↗

PubMed1986

The assessment of the chemotherapeutic effects of vinca alkaloids by immunofluorescence and flow cytometry.

The effects of the vinca alkaloids on the rates of DNA synthesis in the human pancreatic carcinoma line, MIA Pa Ca-2 have been studied by a new technique for measuring cell kinetics and DNA synthesis by flow cytometry and immunofluorescence. The method employs a monoclonal antibody that is highly specific for bromodeoxyuridine or iododeoxyuridine. The drugs vincristine and vindesine do not appear to have a direct effect on DNA synthesis rate across S phase, whereas DHAD, a compound that has been found previously to affect DNA synthesis, does appear by this technique to inhibit DNA synthesis at specific segments of S phase. That vincristine does not block cells in S phase by inhibiting DNA synthesis is borne out of the observation that cells blocked in S or G2 + M can still incorporate BrdUrd at a high rate in these phases of the cell cycle.

Animals↗

PubMed1986

Comparative effects of selected drug combinations on the growth of a human pancreatic carcinoma cell line (MIA PaCa-2).

The inhibitory effect of several drug combinations on the growth of the human pancreatic carcinoma cell line MIA PaCa-2 was studied in relation to drug-scheduling interval in vitro. All drug exposures were for 1 hour. The sequential exposure of cells to 1.5 X 10(-8) M vincristine (VCR) or vindesine (VDS) followed by 2 X 10(-8) M 1,2-dihydroxy-9,10-anthracenedione (DHAD) or 3 X 10(-7) M adriamycin (ADR) had at best an additive effect, demonstrated by isobologram analysis, when the two drugs were given 6 hours apart. Flow cytometry (FCM) analysis after exposure of the cells to the priming drug alone, i.e., VCR or VDS, showed an accumulation of cells in S-phase. The exposure of MIA PaCa-2 cells to 1.6 X 10(-5) M 5-fluorouracil (FUra) followed by 2 X 10(-8) M DHAD or 3 X 10(-7) M ADR had an additive (with DHAD) or synergistic (with ADR) effect when the two drugs were given simultaneously and a synergistic effect with either drug when they were given 2, 6, or 24 hours apart. FCM analysis after exposure to FUra alone showed a rapid S-phase accumulation appearing within 6 hours and increasing further after 24 hours. Sequential exposure of cells to 1.5 X 10(-8) M VCR and 1.6 X 10(-5) M FUra had a synergistic effect, regardless of the sequence or the time interval between the two drugs.

Anthraquinones↗

PubMed1984

Sensitivity of cultured human pancreatic carcinoma cells to dihydroxyanthracenedione.

We tested the effectiveness of dihydroxyanthracenedione (DHAD) on cell growth of two human pancreatic carcinoma cell lines MIA PaCa-2 and PANC-1. At the level of ID50, the drug was almost equally effective against both cell lines. When the time exposure of MIA PaCa-2 cells to the drug was increased from 1 h to continuous exposure for 5 days, the ID50 was decreased about three-fold only (1.4 X 10(-8)M and 4 X 10(-9)M respectively). At the level of ID50 also the difference between 6 h exposure and continuous exposure for 5 days was minimal. In equimolar concentrations and with 1 h exposure, DHAD was more effective against MIA PaCa-2 cells than other chemotherapeutic agents including adriamycin, mitomycin-C, 5-FU, vincristine, vindesine, vinblastine, VP-16-213, bleomycin, cis-platinum, asparaginase and acivicin. In concentrations of 5 X 10(-7)M, DHAD caused about 40% inhibition of 14C-thymidine incorporation of MIA PaCa-2 cells. Treatment of MIA PaCa-2 cells with the ID50 of DHAD for 1 h caused retardation of cellular traverse, with the major effect appearing to be in G2 + M phase of the cycle. From these data DHAD appears to be a potent drug against human pancreatic carcinoma in vitro.

Anthraquinones↗

PubMed1984

Sensitivity of human pancreatic carcinoma cell line (MIA PaCa-2) to Bisantrene and Theprubicin in vitro.

We tested the effect of Bisantrene (BS) and Theprubicin (THP-ADR) on cell growth of a human pancreatic carcinoma cell line (MIA PaCa-2). After 1 h exposure ID50 of BS or THP-ADR was 3 X 10(-7) and 5 X 10(-8) M, respectively. Increasing the exposure time from 1 h to continuous exposure for 5d resulted in 11-fold decrease in ID50 for BS and a 6-fold decrease for THP-ADR. Both drugs inhibited [14C]thymidine incorporation to the same extent and caused an accumulation of cells into G2 + M phase of the cell cycle.

Anthracenes↗